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The purpose of this study was to evaluate bone healing in calvarial defects using two bone graft substitute materials; biphasic beta-tricalcium phosphate/hydroxyapatite in hydrogel (ss-TCP/HA) versus composite non-demineralized xenogenic dentin with ss-TCP/HA mixture. Full thickness critical-sized defects were created bilaterally in 10 New Zealand male rabbits. Seven defects were left empty, six filled with biphasic tricalcium phosphate putty, and seven were filled with composite non-demineralized xenogenic dentin with biphasic tricalcium phosphate. Animals were sacrificed at eight weeks postoperatively and the healing of the biomaterial-filled defects was compared radiographically and by histomorphometry. Micro-computed tomography (CT) was utilized to analyze the osteogenesis and healing patterns of the defects. Quantitative analysis of volume fraction (%) of the newly formed bone and remaining graft material (FV=filling volume/TV=tissue volume) and mean intensity [HU] in the defects were evaluated. Defects filled with composite dentin with biphasic tri-calcium phosphate showed volume fraction (FV/TV) in the order of 55.81% +/- 17.72%, whereas defects filled with only biphasic tricalcium phosphate showed a fraction of 39.84% +/- 16.06%, which represent the ratio of remaining graft material and new bone formation to the tissue volume. The empty negative control defects showed a volume fraction of 19.14% +/- 8.787%. Histological analysis showed significant percentage increase in bone formation and residual graft with the composite Dentin/ss-TCP group after 8 weeks. The findings suggest that composite xenogenic dentin with biphasic tricalcium phosphate showed improved osteogenesis when compared to biphasic tricalcium phosphate without the addition of non-demineralized dentin. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 773-782, 2019.

The liver as transplantation site for pancreatic islets is associated with significant loss of islets, which can be prevented by grafting in a prevascularized, subcutaneous scaffold. Supporting vascularization of a scaffold to limit the period of ischemia is challenging and was developed here by applying liposomes for controlled release of angiogenic factors. The angiogenic capacity of platelet-derived growth factor, vascular endothelial growth factor, acidic fibroblast growth factor (aFGF), and basic FGF were compared in a tube formation assay. Furthermore, the release kinetics of different liposome compositions were tested. aFGF and L-alpha-phosphatidylcholine/cholesterol liposomes were selected to support vascularization. Two dosages of aFGF-liposomes (0.5 and 1.0 mu g aFGF per injection) were administered weekly for a month after which islets were transplanted. We observed enhanced efficacy in the immediate post-transplant period compared to the untreated scaffolds. However, on the long-term, glucose levels of the aFGF treated animals started to increase to diabetic levels. These results suggest that injections with aFGF liposomes do improve vascularization and the immediate restoration of blood glucose levels but does not facilitate the long-term survival of islets. Our data emphasize the need for long-term studies to evaluate potential beneficial and adverse effects of vascularization protocols of scaffolds. (C) 2017 Wiley Periodicals, Inc.

The treatment of bone defects with recombinant bone morphogenetic protein‐2 (BMP‐2) requires high doses precluding broad clinical application. Here, a bioengineering approach is presented that strongly improves low‐dose BMP‐2‐based bone regeneration by mobilizing healing‐associated mesenchymal progenitor cells (MPCs). Smart synthetic hydrogels are used to trap and study endogenous MPCs trafficking to bone defects. Hydrogel‐trapped and prospectively isolated MPCs differentiate into multiple lineages in vitro and form bone in vivo. In vitro screenings reveal that platelet‐derived growth factor BB (PDGF‐BB) strongly recruits prospective MPCs making it a promising candidate for the engineering of hydrogels that enrich endogenous MPCs in vivo. However, PDGF‐BB inhibits BMP‐2‐mediated osteogenesis both in vitro and in vivo. In contrast, smart two‐way dynamic release hydrogels with fast‐release of PDGF‐BB and sustained delivery of BMP‐2 beneficially promote the healing of bone defects. Collectively, it is shown that modulating the dynamics of endogenous progenitor cells in vivo by smart synthetic hydrogels significantly improves bone healing and holds great potential for other advanced applications in regenerative medicine., Engineered biomaterials are used to trap and isolate bone progenitor cells during bone healing. Freshly isolated bone progenitor cells enable the identification of bioactive molecules that stimulate their recruitment. Identified recruitment‐stimulating molecules and bone morphogenetic protein are used to treat bone defects. Only the biomaterials‐controlled sequential, but not the simultaneous delivery of both factors improves bone healing.